Abstract / Project Summary Mild traumatic brain injury (mTBI) is a source of major morbidity in recent veterans who served in Iraq and Afghanistan. There has been keen interest in using diffusion tensor imaging (DTI) to assess white matter damage associated with mTBI. The goal of this proposal is to provide quantitative assessment and visualization of white matter damage in a single subject that is based on comparison to a large reference group of non-TBI veterans. Our approach involves performing a whole-brain analysis to create an FA (fractional anisotropy) map that is suggestive of white matter injury in a single subject by comparison to mean FA from a reference group of 100 subjects. We propose primary and confirmatory analytic methods for significance testing: (i) using a method of non-parametric statistics known as permutation testing followed by a novel threshold-free correction for multiple comparison testing, and (ii) using population based inferential statistics to compute whole brain Z-statistic map followed by more typical cluster-based correction for multiple comparisons. Our preliminary data suggests that white matter damage can be effectively assessed in single subjects. Thus, our proposal moves beyond the conventional application of DTI to mTBI research for making group comparisons. If successful and then confirmed in a larger scale study, the approach we propose would provide objective evidence of injury for diagnosing individual patients with mTBI in the clinical setting.